Obstetric factors and neonatal outcomes of depressed skull fractures in newborns.

PURPOSE: To determine the obstetric factors affecting the development of depressed skull fracture in neonates. MATERIALS AND METHODS: This was a retrospectively cohort study on neonates born between July 2016 and August 2021. Neonates diagnosed with depressed skull fractures within one week of birth through X-ray and/or brain ultrasonography were included, and their mothers' obstetric characteristics were reviewed. RESULTS: There were 12 cases in 6791 live births. Five women were over 35 years old. All except two were nulliparous. Five cases were delivered from labor induction and others presented with spontaneous labor. Except for two cases, delivery occurred within an hour after full cervical dilatation. Two cases were assisted by vacuum. None displayed fetal distress signs such as low Apgar scores below 7, meconium staining, and umbilical cord pH under 7.2. All depressed fractures were found in the right parietal area. Three cases resulted in focal hyperechoic lesion in brain ultrasonography and two of them showed small hemorrhage-like lesion in magnetic resonance imaging. All depressed skull fractures improved within 6 months in followed X-rays or ultrasonography. CONCLUSIONS: There was no definitely associated obstetric condition for depressed skull fracture of neonates although nulliparous women were majority of the affected cases.

Degree of expression of inflammatory proteins in the amniotic cavity, but not prior obstetric history, is associated with the risk severity for spontaneous preterm birth after rescue cerclage for cervical insufficiency.

PROBLEM: To examine whether the severity of spontaneous preterm birth (SPTB) risk after rescue cerclage for acute cervical insufficiency (CI) is linked to the degree of inflammatory response in the amniotic fluid (AF) based on the concentrations of various inflammatory proteins and prior obstetric history. METHOD OF STUDY: We conducted a retrospective cohort study of 65 singleton pregnant women (17-25 weeks) who underwent rescue cerclage following the diagnosis of acute CI and were subjected to amniocentesis. EN-RAGE, IL-6, IL-8, and IP-10 as inflammatory mediators and kallistatin, MMP-2/8, and uPA as extracellular matrix remodeling-related molecules were assayed in the AF using ELISA. The level of each inflammatory mediator was divided into quartiles. RESULTS: Intra-amniotic inflammation (IAI; AF IL-6 level ≥2.6 ng/mL) was independently associated with SPTB after cerclage placement. The odds of SPTB at < 32 weeks, even after adjusting for confounders, increased significantly with each increasing quartile of baseline AF levels for each inflammatory mediator (p for trend < .05). Kaplan-Meier survival curves showed that the cerclage-to-delivery intervals were significantly shorter as the quartiles of AF EN-RAGE and MMP-8 increased (log-rank test, p < .01 each). Neither previous term birth nor prior PTB was associated with SPTB risk or cerclage-to-delivery interval after rescue cerclage. Multiparous women who experience CI after term birth showed significantly elevated levels of MMP-8 and reduced kallistatin levels in the AF. CONCLUSION: In patients with CI, SPTB risk (especially risk severity) after rescue cerclage is associated with the degree of the inflammatory response in AF as well as the presence of IAI but not with prior obstetric history.

Extracellular matrix-related and serine protease proteins in the amniotic fluid of women with early preterm labor: Association with spontaneous preterm birth, intra-amniotic inflammation, and microbial invasion of the amniotic cavity.

PROBLEM: We aimed to determine whether altered levels of various extracellular matrix (ECM)-related and serine protease proteins in the amniotic fluid (AF) are associated with imminent spontaneous preterm birth (SPTB; ≤7 days) and intra-amniotic inflammation and/or microbial invasion of the amniotic cavity (IAI/MIAC) in women with early preterm labor (PTL). METHOD OF STUDY: This retrospective cohort study included 252 women with singleton pregnancies undergoing transabdominal amniocentesis who demonstrated PTL (24-31 weeks). The AF was cultured for microorganism detection to characterize MIAC. IL-6 concentrations were determined in the AF samples to identify IAI (≥2.6 ng/mL). The following mediators were measured in the AF samples using ELISA: kallistatin, lumican, MMP-2, SPARC, TGFBI, and uPA. RESULTS: Kallistatin, MMP-2, TGFBI, and uPA levels were significantly higher and SPARC and lumican levels were significantly lower in the AF of women who spontaneously delivered within 7 days than in the AF of those who delivered after 7 days; the levels of the first five mediators were independent of baseline clinical variables. In the multivariate analysis, elevated levels of kallistatin, MMP-2, TGFBI, and uPA and low levels of lumican and SPARC in the AF were significantly associated with IAI/MIAC and MIAC, even after adjusting for the gestational age at sampling. The areas under the curves of the aforementioned biomarkers ranged from 0.58 to 0.87 for the diagnoses of each of the corresponding endpoints. CONCLUSION: ECM-related (SPARC, TGFBI, lumican, and MMP-2) and serine protease (kallistatin and uPA) proteins in the AF are involved in preterm parturition and regulation of intra-amniotic inflammatory/infectious responses in PTL.

A Comparison of Ultrasound Imaging Texture Analyses During the Early Postpartum With the Mode of Delivery.

BACKGROUND: Breastfeeding is beneficial to infants. However, cesarean section is reported to be a risk factor for unsuccessful breastfeeding. RESEARCH AIMS: (1) To extract discriminating data from texture analysis of breast ultrasound images in the immediate postpartum period; and (2) to compare the analysis results according to delivery mode. METHODS: A cross-sectional, prospective non-experimental design with a questionnaire and observational components was used. Participants (N = 30) were women who delivered neonates at a center from September 2020 to December 2020. The participants underwent ultrasound examination of bilateral breasts 7-14 days after delivery. Ultrasound images were collected for texture analysis. A questionnaire about breastfeeding patterns was given to the participants on the day of the ultrasound examination. RESULTS: No significant differences were found in texture analysis between the breasts of participants who had undergone Cesarean section and vaginal deliveries. The mean volume of total human milk produced in 1 day was significantly greater in the vaginal delivery group than in the cesarean section group (M = 350.87 ml, SD = 183.83 vs. M = 186.20 ml, SD = 184.02; p = .017). The pain score due to breast engorgement measured subjectively by participants was significantly lower in the vaginal delivery group than in the cesarean section group (M = 2.8, SD = 0.86 vs. M = 3.4, SD = 0.63; p = .047). CONCLUSION: Texture analysis of breast ultrasound images did not demonstrate difference between the cesarean section and vaginal delivery groups in the immediate postpartum period; nevertheless, cesarean section was independently associated with less successful breastfeeding.

Plasma IGFBP-1, Fas, kallistatin, and P-selectin as predictive biomarkers of histologic chorioamnionitis and associated intra-amniotic infection in women with preterm labor.

PROBLEM: To determine whether altered levels of 13 plasma biomarkers, alone or in combination, could be independently associated with histologic chorioamnionitis (HCA) and microbial-associated HCA (defined as the presence of HCA along with microbial invasion) in women with preterm labor (PTL). METHODS OF STUDY: This was a retrospective cohort study involving 77 singleton pregnant women with PTL (23-34 gestational weeks) who delivered within 96 h of plasma and amniotic fluid (AF) sampling. DKK-3, E-selectin, Fas, haptoglobin, IGFBP-1, kallistatin, MMP-2, MMP-8, pentraxin 3, progranulin, P-selectin, SAA4, and TGFBI levels were assayed in plasma samples by ELISA. AF obtained via amniocentesis was used for microorganism identification. RESULTS: Multiple logistic regression analyses revealed significant associations between low plasma IGFBP-1 levels and acute HCA, and between low plasma Fas and kallistatin levels, and elevated plasma P-selectin levels and microbial-associated HCA (all p < .05), after adjusting for gestational age. Using a stepwise regression procedure, a multi-biomarker panel for microbial-associated HCA was developed, which included plasma MMP-2, kallistatin, and P-selectin levels (area under the curve [AUC], .867). The AUC for this three-marker panel was significantly or borderline significantly greater than that of any single variable included in the panel. However, a predictive model for acute HCA could not be developed because only one variable (MMP-2) was selected. CONCLUSIONS: These findings demonstrate that IGFBP-1, Fas, kallistatin, and P-selectin are associated with acute HCA and microbial-associated HCA in women with PTL. Their combined use can significantly improve the diagnostic ability for the detection of microbial-associated HCA.

Association between in vitro fertilisation embryo transfer and placental pathology in women with preterm birth: a retrospective cohort study.

CONTEXT: The number of women who achieve pregnancy through assisted reproductive technology (ART), including in vitro fertilisation and embryo transfer (IVF-ET), is increasing worldwide. Placenta-mediated diseases associated with ART, such as gestational hypertension, preeclampsia, disorders of placental implantation, and placental abruption, are also increasing. AIMS: To determine the association between placental pathologies and IVF-ET in women with preterm births. METHODS: This retrospective cohort study examined archived placenta specimens of women who achieved pregnancy through either spontaneous conception or IVF-ET. In total, 1677 women with singleton pregnancies who gave birth consecutively between 20 and 37weeks of gestation at Seoul National University Bundang Hospital and underwent placental pathologic evaluation between April 2013 and October 2018 were included. Data from all pathologic reports were reviewed. KEY RESULTS: The IVF-ETgroup had a higher median maternal age and rate of nulliparity than the natural conception group. The incidence rate of obstetric complications, except preterm premature rupture of membranes and placenta previa, was similar in both groups. The IVF-ET group had a higher incidence rate of placental infarction than the natural conception group (26.4% vs 16.4%, P =0.012). Multivariate logistic regression analysis indicated that IVF, hypertensive disorders, and fetal growth restriction were significantly associated with placental infarction. CONCLUSIONS: IVF-ET was independently associated with the risk of placental infarction in women with preterm births. IMPLICATIONS: The use of IVF-ET may cause abnormal placental formation with an increased risk of anatomical and vascular pathology, which are observed in preterm deliveries and may contribute to pregnancy complications.

Plasma E-selectin and kallistatin as predictive markers of histologic chorioamnionitis in women with preterm premature rupture of membranes.

PROBLEM: We aimed to assess the predictive potential of 12 plasma biomarkers to predict acute histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM) and to develop multi-biomarker panels based on these biomarkers in combination with widely used conventional laboratory markers. METHOD OF STUDY: This was a retrospective cohort study involving 81 singleton pregnant women (24-34 weeks of gestation) who delivered within 96 h of blood sampling. White blood cell (WBC) count, differential counts, and C-reactive protein (CRP) levels were measured at admission. The levels of DKK-3, Fas, haptoglobin, IGFBP-2, kallistatin, MIP-1α, MMP-2, MMP-8, pentraxin 3, progranulin, E-selectin, and P-selectin were evaluated by ELISA using stored plasma samples. The primary outcome measure was acute HCA. RESULTS: Multivariate analyses showed that low plasma E-selectin and kallistatin levels were independently associated with HCA occurrence after adjusting for gestational age. Using a stepwise regression analysis, a multi-biomarker panel comprising plasma E-selectin, serum CRP, and WBC was developed, which provided a good prediction of acute HCA in women with PPROM (area under the curve [AUC], 0.899), with a significantly higher AUC than that of any single variable included in the panel (P < 0.05). The plasma levels of DKK-3, Fas, haptoglobin, IGFBP-2, MIP-1α, MMP-2, MMP-8, pentraxin 3, and P-selectin were not significantly associated with HCA occurrence. CONCLUSIONS: This study identified E-selectin and kallistatin as potential plasma biomarkers associated with acute HCA in women with PPROM. Their combined analysis with serum CRP and WBC counts significantly improved acute HCA diagnosis.

Lamellar body count: Marker for foetal lung maturation promoted by intra-amniotic infection and/or inflammation.

OBJECTIVE: There is evidence indicating that the risk of respiratory distress syndrome is reduced in preterm neonates exposed to intra-amniotic infection and/or inflammation. We hypothesised that foetal lung maturation promoted by intra-amniotic infection and/or inflammation results in elevated lamellar body count (LBC) in amniotic fluid (AF). This study aimed to determine the relationship between LBC in AF and intra-amniotic infection and/or inflammation in patients with threatened preterm birth. STUDY DESIGN: This was a retrospective cohort study of patients with threatened preterm birth. A total of 104 consecutive pregnant women underwent amniocentesis in the early preterm period [gestational age < 34 weeks] to evaluate intra-amniotic infection and/or inflammation and foetal lung maturity. Intra-amniotic infection was confirmed by positive AF culture results for aerobic/anaerobic bacteria, fungi, and genital mycoplasma. Intra-amniotic inflammation was defined as a positive AF matrix metalloproteinase-8 rapid test. Outcomes of the study population were compared according to LBC in AF using a cut-off of 15,000/mm3. RESULTS: The rates of elevated LBC and intra-amniotic infection and/or inflammation were 23% (24/104) and 52% (54/104), respectively. The median LBC was significantly higher in patients with intra-amniotic infection and/or inflammation than in those without [median LBC, 9,000/mm3 (interquartile range, IQR: 3,000-39,000) vs. 3,000/mm3 (IQR: 2,750-5,000), p < 0.001]. Intra-amniotic infection and/or inflammation was observed in 96% (23/24) of patients with elevated LBC and 39% (31/80) of patients without elevated LBC (p < 0.001). On multivariable analysis, the presence of intra-amniotic infection and/or inflammation was significantly associated with elevated LBC with an odds ratio (OR) of 66.0 [95% confidence interval (CI) 6.6-664.4, p < 0.001], even after accounting for gestational age at amniocentesis being a significantly related factor for predicting elevated LBC with an OR of 1.5 (95% CI 1.1-2.0, p = 0.004). CONCLUSION: LBC elevation was independently associated with the presence of intra-amniotic infection and/or inflammation in women with early threatened preterm birth (gestational age < 34 weeks). This finding may support the view that an intra-amniotic inflammatory response promotes foetal lung maturation that can be detected by elevated LBC in AF.

The association between maternal pre-pregnancy body mass index and pregnancy outcomes of preeclampsia.

OBJECTIVE: To evaluate the effects of pre-pregnancy maternal body mass index (BMI) to pregnancy outcomes in patients diagnosed as preeclampsia. MATERIALS AND METHODS: This was a retrospectively study on women who had been diagnosed as preeclampsia and delivered at Seoul National University Bundang Hospital between June 2017 and March 2020. Multifetal gestation, major fetal anomaly, and fetal death in utero were excluded. A total of 150 singleton pregnancies were included and divided into four groups according to the pre-pregnancy BMI classification: underweight (<18.5 kg/m2, n = 6), normal (18.5-22.9 kg/m2, n = 66), overweight (23.0-24.9 kg/m2, n = 26), and obese (≥25.0 kg/m2, n = 52). Pregnancy outcomes including gestational age at delivery, birthweight, and delivery modes were reviewed. RESULTS: The rates of preterm birth before 34 weeks of gestation were 67%, 49%, 35%, and 27% for underweight group, normal BMI group, overweight group, and obese group, respectively (p-trend = 0.006). The birthweight of newborn increased significantly as pre-pregnancy BMI increased (p-trend<0.001). The proportions of small for gestational age (SGA) were highest in underweight group and decreased as pre-pregnancy BMI increased (67%, 41%, 42%, and 10% for each group, respectively, p-trend<0.001). CONCLUSION: The rates of preterm birth before 34 weeks and SGA increased as pre-pregnancy BMI decreased in patients with preeclampsia. IMPLICATIONS FOR PRACTICE: Women with underweight before pregnancy are at the highest risk for preterm birth and SGA, therefore they need to be monitored more intensively when diagnosed as preeclampsia.

Prediction of emergency cerclage outcomes in women with cervical insufficiency: The role of inflammatory, angiogenic, and extracellular matrix-related proteins in amniotic fluid.

OBJECTIVE: We aimed to determine whether various novel inflammatory, angiogenic, and extracellular matrix-related mediators in amniotic fluid (AF) can independently predict emergency cerclage outcomes in women with acute cervical insufficiency (CI). METHODS: This was a retrospective cohort study conducted among 50 singleton pregnant women (18-25 weeks) who underwent emergency cerclage for CI and were subjected to amniocentesis. The AF samples were assayed for endoglin, endostatin, haptoglobin, insulin-like growth factor-binding protein (IGFBP)-3, -4, kallistatin, lumican, macrophage colony-stimulating factor (M-CSF), pentraxin 3, p-selectin, receptor for advanced glycation end products (RAGE), resistin, transforming growth factor beta-induced (TGFBI), and vitamin D-binding protein (VDBP) levels. Interleukin (IL)-6 levels in the AF were also measured for comparison with potential biomarkers assessed in this study. The primary endpoint was spontaneous preterm delivery (SPTD) at <34 weeks following emergency cerclage. RESULTS: The AF levels of pentraxin 3, RAGE, and resistin were significantly higher in women who had SPTD at <34 weeks after cerclage placement (pentraxin-3: P = 0.003; RAGE: P = 0.041; and resistin; P = 0.002). In multivariate analysis, elevated AF levels of pentraxin 3 (P = 0.007) and resistin (P = 0.006), but not those of RAGE (P = 0.069), were independently associated with the occurrence of SPTD at <34 weeks after cerclage, following adjustment for baseline clinical variables (e.g., cervical dilation). The area under the curve (AUC) values of AF pentraxin 3, RAGE, and resistin for the prediction of SPTD at <34 weeks were 0.749, 0.669, and 0.770, respectively, which were similar to those of AF IL-6. However, in univariate analyses, no differences in the AF levels of endoglin, endostatin, haptoglobin, IGFBP-3, IGFBP-4, kallistatin, lumican, p-selectin, TGFBI, and VDBP were found to be associated with SPTD at <34 weeks after cerclage placement. CONCLUSIONS: In women with acute CI, the AF levels of pentraxin 3, RAGE, and resistin could be useful novel biomarkers for predicting SPTD following emergency cerclage. However, the clinical utility of these new biomarkers should be validated in larger multicenter studies.

Antibody microarray analysis of amniotic fluid proteomes in women with cervical insufficiency and short cervix, and their association with pregnancy latency length.

INTRODUCTION: This study aimed to investigate amniotic fluid (AF) proteins that were differentially expressed between patients with cervical insufficiency (CI) and asymptomatic short cervix (SCX, ≤ 25 mm), and whether these proteins could be predictive of spontaneous preterm birth (SPTB) in these patients. METHOD: This was a retrospective cohort study of 129 singleton pregnant women with CI (n = 80) or SCX (n = 49) at 17 to 26 weeks who underwent amniocentesis. An antibody microarray was used to perform comparative proteomic profiling of AF from matched CI (n = 20) and SCX (n = 20) pregnancies. In the total cohort, an ELISA validation study was performed for 15 candidate proteins of interest. Subgroup analyses of patients with CI and SCX were conducted to evaluate the association between the 15 proteins and SPTB at < 32 weeks of gestation. RESULTS: Eighty-six proteins showed intergroup differences. ELISA validation confirmed significantly higher levels of AF EN-RAGE, IL-8, lipocalin-2, MMP-9, S100A8/A9, thrombospondin-2, and TNFR2 in patients with CI than in those with SCX. Multivariable analysis showed that increased AF levels of EN-RAGE, S100A8/A9, and uPA were independently associated with SPTB at < 32 weeks in patients with CI; whereas in patients with SCX, high AF levels of APRIL, EN-RAGE, LBP, and TNFR2 were independently associated with SPTB at < 32 weeks. CONCLUSIONS: Multiple AF proteins show altered expression in patients with CI compared with SCX controls. Moreover, several novel mediators involved in inflammation were identified as potential biomarkers for predicting SPTB after the diagnosis of CI and SCX. These results provide new insights into target-specific molecules for targeted therapies to prevent SPTB in patients with CI/SCX.

Use of continuous infusion of nicardipine to control persistent postpartum hypertension: A retrospective study.

To evaluate the effect of continuous infusion of nicardipine on the management of uncontrolled blood pressure (BP) during postpartum period. This retrospective study included 209 women diagnosed in hospital with hypertensive disorders during pregnancy and had uncontrolled BP after delivery between January 2018 to December 2020 Uncontrolled BP was defined as persistent elevation of systolic BP ≥ 160 mm Hg or diastolic BP ≥ 110 mm Hg. Patients were divided into 2 groups: nicardipine (N = 53; continuous nicardipine infusion and additional bolus of labetalol or hydralazine) and control (N = 156; consecutive bolus of labetalol or hydralazine). BP data were analyzed using the Mann-Whitney U and χ2 tests by dividing the time interval of 4 hours by the delivery time. The highest BP trends showed that the mean values of both systolic and diastolic BP immediately before delivery were higher in the nicardipine group than in the control. After 8 to 12 hours following delivery, both systolic and diastolic BP were lower in the nicardipine group than in the control. Subsequently, 16 to 20 hours after delivery, both systolic and diastolic BP were significantly lower in the nicardipine group than in the control (137/80 vs 141/84 mm Hg). Initially, the proportions of uncontrolled BP in the nicardipine group were higher than those in the control; however, it then became lower at all time intervals 8 hours after delivery. The proportions of patients who received additional antihypertensive agents and the median cumulative dosages were lower in the nicardipine group than in the control. Continuous infusion of nicardipine can help manage uncontrolled BP during the postpartum period.